Qualitative Analysis of Perspectives on Lung Transplant among People with Cystic Fibrosis.

RATIONALE: Lung transplant (LTx) is a potentially life-saving treatment option for individuals with advanced cystic fibrosis (CF), but more people with CF (PwCF) and advanced lung disease die each year than undergo transplant in the United States. Little is known about these individuals' LTx information needs and factors influencing their decision-making process related to transplant. OBJECTIVES: To examine PwCF's experiences with, and preferences for, provision of LTx information; to identify transplant information needs that CF clinicians are well-positioned to address. METHODS: We performed semi-structured qualitative interviews in two separate cohorts: PwCF without LTx and PwCF with LTx between July 2019 and June 2020. Questions focused on awareness and knowledge about LTx, perspectives related to communication about transplant in CF clinic, and experiences with LTx. Thematic analysis was utilized to organize the qualitative data. Exemplar quotes were chosen to illustrate domains that emerged pertaining to the research objectives. RESULTS: Fifty-five PwCF, 35 without LTx and 20 with LTx, participated. One-third of PwCF without LTx had normal or near-normal lung function. Key common domains among PwCF with and without LTx were identified including information needs, connections with LTx recipients, and conversations with CF clinicians. For PwCF with and without transplant, concrete information needs were identified: success or survival, social support, surgery, recovery/pain, and quality of life post-transplant. The importance of connecting with LTx recipients to hear their stories and experiences was emphasized by both PwCF with and without transplant. Important considerations for timing and content of discussions with CF clinicians were identified, including having information presented early (before LTx referral is needed) and in limited detail at first. PwCF without LTx wanted to understand how LTx was relevant to them, with a focus on the unique experience of CF. PwCF with LTx emphasized the need for a centralized resource for LTx information. CONCLUSIONS: The findings provide content areas for CF clinicians to focus on as they proactively initiate conversations about LTx and support the development of tools to aid in discussions about LTx for PwCF.

A longitudinal analysis of respiratory symptoms in people with cystic fibrosis with advanced lung disease on and off ETI.

People with CF (PwCF), particularly those with advanced lung disease (ALD), experience frequent respiratory symptoms. A major CF breakthrough was the approval of elexacaftor/tezacaftor/ivacaftor (ETI) in 2019, which has been shown to improve symptoms and lung function in the CF population, and decrease pulmonary exacerbations. The purpose of this study was to analyze longitudinal changes in respiratory symptoms over 24 months in ETI-treated and untreated PwCF with ALD Symptoms were measured among CF adults with ppFEV1 < 40% (N = 48, 24 ETI-treated, 24 untreated) using the CFRSD-CRISS and the CFQ-R [respiratory]. Two multilevel growth models assessed the rate of change in symptoms overall and within the ETI-treated and untreated groups. PwCF on ETI had significantly lower symptom severity over 24 months than those not on ETI as measured by the CRISS and CFQ-R. The ETI-treated group maintained an -11.7 and +19.3 point difference(p<0.01) in CRISS and CFQ-R scores over the study compared to the non-ETI group, achieving minimal clinically important differences on average between groups on both instruments. No change in the symptom burden trajectory between groups was observed (p = 0.58). Even with ALD, ETI-treated PwCF have a lower respiratory burden than those not on ETI. This may be confounded by survivorship bias in the non-ETI group. Of note, in this ALD cohort, neither instrument demonstrated ceiling effects. Our results suggest that, while ETI has significantly improved the lived experience, PwCF with ALD are still plagued by respiratory symptoms.

Lung Allocation Score Exceptions in Persons with Cystic Fibrosis Undergoing Lung Transplant.

Rationale: Lung transplantation can extend the lives of individuals with advanced cystic fibrosis (CF). Until March 2023, the Lung Allocation Score (LAS) was used in the United States to determine transplant priority. Certain clinical events or attributes ("risk events") that are not included in the LAS (e.g., massive hemoptysis) are relatively common and prognostically important in CF and may prompt an exception request to increase priority for donor lungs. The new Lung Composite Allocation Score (CAS) also allows for exceptions based on the same principles. Objectives: To evaluate the frequency of LAS exceptions in persons with CF (PwCFs) listed for lung transplantation and assess whether LAS exceptions are associated with improved waitlist outcomes for PwCFs compared with similarly "at-risk" individuals without LAS exceptions. Methods: A merged dataset combining data from the CF Foundation Patient Registry and the Organ Procurement and Transplantation Network (2005-2019) was used to identify PwCFs listed for lung transplantation. We compared waitlist outcomes between PwCFs with a LAS exception versus those without an exception despite having a risk event. Risk events were defined as an episode of massive hemoptysis, pneumothorax, at least three moderate/severe pulmonary exacerbations, and/or a decrease in forced expiratory volume in 1 second by ⩾30% predicted (absolute) in the prior 12 months. Analyses were performed using competing risk regression with time to transplantation as the primary outcome and death without a transplant as a competing risk. Results: Of 3,538 listings from 3,309 candidates, 2% of listings (n = 81) had at least one exception. Candidates with an exception and those with a risk event but no exception received lung transplants more slowly than people without an exception or risk event (subdistribution hazard ratio [95% confidence interval]: LAS exception cohort, 0.66 [0.52-0.85]; risk event cohort without exceptions, 0.79 [0.72-0.86]). There was no difference between those with LAS exceptions and those at risk without LAS exceptions: subdistribution hazard ratio, 0.84 (0.66-1.08). Conclusions: LAS exceptions are rare in PwCFs listed for lung transplantation. LAS exceptions resulted in a similar time to transplantation for PwCFs compared with similarly at-risk individuals. As we enter the CAS era, these LAS-based results are pertinent to improve risk stratification among PwCFs being considered for lung transplantation.

Patient perspectives on elexacaftor/tezacaftor/ivacaftor after lung transplant.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators, including elexacaftor/tezacaftor/ivacaftor (ETI), significantly improve outcomes and quality of life for people with cystic fibrosis (CF). However, little is known about how lung transplant recipients (LTRs) perceive the use of ETI. We conducted a survey to assess perspectives on ETI among LTRs with CF at our lung transplant program. Of 81 CF LTRs, 46 participants (58 %) responded. The majority of respondents (88 %) were aware of ETI. Over 80 % considered treating non-lung symptoms of CF to be very important. Concerns regarding ETI included potential drug interactions with transplant medications (77 %), side effects (53 %), cost of medication (49 %), and lack of clinical trial data for LTRs (43 %). Half reported they would only consider taking ETI if their CF or transplant doctor recommended it. The findings suggest that CF LTRs seek informational support and shared decision-making about ETI from their clinicians.

Computed tomography body composition and clinical outcomes following lung transplantation in cystic fibrosis.

BACKGROUND: Low muscle mass is common in patients approaching lung transplantation and may be linked to worse post-transplant outcomes. Existing studies assessing muscle mass and post-transplant outcomes include few patients with cystic fibrosis (CF). METHODS: Between May 1993 and December 2018, 152 adults with CF received lung transplants at our institution. Of these, 83 met inclusion criteria and had usable computed tomography (CT) scans. Using Cox proportional hazards regression, we evaluated the association between pre-transplant thoracic skeletal muscle index (SMI) and our primary outcome of death after lung transplantation. Secondary outcomes, including days to post-transplant extubation and post-transplant hospital and intensive care unit (ICU) length of stay, were assessed using linear regression. We also examined associations between thoracic SMI and pre-transplant pulmonary function and 6-min walk distance. RESULTS: Median thoracic SMI was 26.95 cm2/m2 (IQR 23.97, 31.32) for men and 22.83 cm2/m2 (IQR 21.27, 26.92) for women. There was no association between pre-transplant thoracic SMI and death after transplant (HR 1.03; 95% CI 0.95, 1.11), days to post-transplant extubation, or post-transplant hospital or ICU length of stay. There was an association between pre-transplant thoracic SMI and pre-transplant FEV1% predicted (b = 0.39; 95% CI 0.14, 0.63), with higher SMI associated with higher FEV1% predicted. CONCLUSIONS: Skeletal muscle index was low for men and women. We did not identify a significant relationship between pre-transplant thoracic SMI and post-transplant outcomes. There was an association between thoracic SMI and pre-transplant pulmonary function, confirming the potential value of sarcopenia as a marker of disease severity.

The Lung Transplant Candidate, Indications, Timing, and Selection Criteria.

Lung transplantation can be lifesaving for patients with advanced lung disease. Demographics are evolving with recipients now sicker but determining candidacy remains predicated on one's underlying lung disease prognosis, along with the likelihood of posttransplant success. Determining optimal timing can be challenging, and most programs favor initiating the process early and proactively to allow time for patient education, informed decision-making, and preparation. A comprehensive, multidisciplinary evaluation is used to elucidate disease progrnosis and identify risk factors for poor posttransplant outcomes. Candidacy criteria vary significantly by center, and close communication between referring and transplant providers is necessary to improve access to transplant and outcomes.

Take on transplant: human-centered design of a patient education tool to facilitate informed discussions about lung transplant among people with cystic fibrosis.

OBJECTIVE: Lung transplant (LTx) saves lives in cystic fibrosis (CF). However, many potential candidates express uncertainty about LTx and die before receiving this treatment. CF guidelines recommend LTx education and clinical discussions well before the need for LTx arises, but limited patient resources exist. MATERIALS AND METHODS: We engaged people with CF and CF physicians in human-centered design of "Take On Transplant" (TOT), a web-based education tool to prepare patients for LTx discussions. Across 3 phases, needs assessment, design groups, and iterative user testing of TOT, we refined TOT from wireframe prototypes, to an interactive website, to a fully functional intervention ready for clinical trials. RESULTS: Fifty-five people with CF and 105 physicians identified information needs to prepare for LTx discussions. Design groups (n = 14 participants) then established core requirements: didactic education ("Resource Library"), patient narratives ("CF Stories"), frequently asked questions ("FAQ"), and self-assessment to tailor content ("My CF Stage"). Iterative usability testing (n = 39) optimized the design of CF Stories and prototype layout. We then developed the TOT website and demonstrated feasibility and preliminary efficacy of use through 2-week field testing (n = 9). DISCUSSION: Our human-centered design process provided guidance for educational tools to serve the evolving needs of potential LTx candidates. Our findings support the process of patient deliberation as a foundation for shared decision-making in CF, and inform educational tools that could potentially translate beyond LTx. CONCLUSION: TOT fills a critical gap in preparing people with CF for shared decision-making about LTx and may serve as a model for educational tools for other preference-sensitive decisions.

Combined assessment of Epstein-Barr virus viral capsid antigen and Epstein-Barr virus nuclear antigen-1 serology for post-transplant lymphoproliferative disorder risk stratification in adult solid organ transplant recipients.

BACKGROUND: Epstein-Barr virus (EBV) seronegative solid organ transplant recipients (SOTRs) are at increased risk for post-transplant lymphoproliferative disorder (PTLD). Assays for EBV serostatus assess antibody to both EBV viral capsid antigen (VCA) and Epstein-Barr nuclear antigen-1 (EBNA-1), but PTLD risk among SOT recipients with discordant VCA and EBNA-1 results is unknown. METHODS: We performed a retrospective, single-center cohort study to determine the risk of PTLD among adult (≥ 18 years) SOTRs with discordant pre-transplant VCA and EBNA-1 IgG compared to that of SOTRs with concordantly negative or concordantly positive serology using univariable and multivariable Cox-proportional hazards models. RESULTS: Of 4106 SOTRs, the number (%) who were concordantly positive, concordantly negative, and discordant was 3787 (92.2%), 149 (3.6%), and 170 (4.2%), respectively. The adjusted hazard of PTLD was significantly higher among discordant SOTRs compared to concordantly positive SOTRs (aHR 2.6, 95% CI 1.04-6.6, p =.04) and lower compared to concordantly negative SOTRs (aHR 0.27, 95% CI 0.10-0.76, p <.001). The adjusted hazard of EBV+ PTLD among those with discordant serology was also significantly higher compared to the concordantly positive cohort (aHR 3.53, 95% CI 1.04-12.0, p =.04) and significantly lower compared to the concordantly negative cohort (aHR 0.23, 95% CI 0.06-0.82, p =.02). CONCLUSIONS: Risk of PTLD among SOTRs with discordant VCA and EBNA-1 may be intermediate between those with concordantly positive and negative serology. If confirmed in future studies, revision of national EBV serology reporting to include both VCA and EBNA results may be needed to optimize PTLD risk stratification.

Development and Internal Validation of a Prognostic Model of the Probability of Death or Lung Transplantation Within 2 Years for Patients With Cystic Fibrosis and FEV1 ≤ 50% Predicted.

BACKGROUND: Improved methods are needed to risk-stratify patients with cystic fibrosis (CF) and reduced FEV1. RESEARCH QUESTIONS: What are the predictors of death or lung transplantation (LTx) within 2 years among patients with CF whose FEV1 ≤ 50% predicted? Do these markers similarly predict outcomes among G551D patients taking ivacaftor since 2012? STUDY DESIGN AND METHODS: Patients with CF, age ≥ 6 years with FEV1 ≤ 50% predicted as of December 31, 2014, were identified in a data set that merged Cystic Fibrosis Foundation and United Network for Organ Sharing (UNOS) registries. The least absolute shrinkage and selection operator (LASSO) method was applied to a randomly selected training set to select important prognostic variables. Accuracy and association of the model with death or LTx with 2 years (2-year death or LTx) were validated via logistic regression on an independent test set. Sensitivity analyses explored predictors for patients with UNOS data. RESULTS: FEV1 percent predicted (OR, 1.51 for 5% decrease; 95% CI, 1.27-1.81), number of pulmonary exacerbations treated with IV antibiotics (OR, 1.35; 95% CI, 1.11-1.65), and continuous or nocturnal oxygen (OR, 3.71; 95% CI, 1.81-7.59) were significantly associated with 2-year death or LTx. Our model predicted outcomes with greater sensitivity (ratio of sensitivity, 1.26; 95% CI, 1.02-1.54), ratio of positive predictive value (1.25; 95% CI, 1.05-1.51), and ratio of negative predictive value (1.04; 95% CI, 1.01-1.07) than FEV1 < 30% predicted. Among those taking ivacaftor in 2014, only FEV1 remained associated with 2-year death or LTx. For patients with UNOS data, LASSO identified additional covariates of interest, including noninvasive ventilation use, low hemoglobin, pulmonary arterial systolic pressure, supplemental oxygen, mechanical ventilation, FEV1 percent predicted, and cardiac index. INTERPRETATION: Among individuals with CF and FEV1 ≤ 50% predicted, FEV1 percent predicted, oxygen therapy, and number of pulmonary exacerbations predicted 2-year death or LTx. Although limited by small sample size, only FEV1 remained predictive in patients receiving highly effective modulator therapy. Additional physiologic variables could improve prognostication in CF.

Hemoptysis and the Risk for Lung Transplant or Death without Transplant in Individuals with Cystic Fibrosis in the United States.

Rationale: Hemoptysis is a common and important complication in persons with cystic fibrosis (PwCF). Despite this, there is limited literature on the impact of hemoptysis on contemporary cystic fibrosis (CF) outcomes. Objectives: Evaluate whether hemoptysis increases the risk of lung transplant or death without a transplant in PwCF. Methods: We reviewed a dataset of PwCF ages 12 years or older from the CFFPR (CF Foundation Patient Registry) that included 29,587 individuals. We identified hemoptysis as our predictor of interest and categorized PwCF as either no hemoptysis, any hemoptysis (submassive and/or massive), or massive hemoptysis. We subsequently evaluated whether hemoptysis, as defined above, was associated with death without transplant or receipt of lung transplant via logistic regression. We adjusted for age, sex, body mass index, forced expiratory volume in one second (FEV1), number of exacerbations, supplemental oxygen use, CF-related diabetes, and Pseudomonas aeruginosa colonization status. Subgroup analyses were performed in advanced lung disease, defined as PwCF with an FEV1 <40% predicted. Results: PwCF with any form of hemoptysis were more likely to progress to lung transplant or die without transplant than PwCF who did not have hemoptysis (odds ratio [OR], 1.3 [95% confidence interval (CI), 1.1-1.7]). The effect size of these associations was larger when hemoptysis events were classified as "massive" (massive hemoptysis OR, 2.2 [95% CI, 1.2-3.8]) or in PwCF with advanced lung disease (massive hemoptysis in advanced lung disease OR, 3.2 [95% CI 1.3-8.2]). Conclusions: Hemoptysis is associated with an increased risk of lung transplant and death without a transplant in PwCF, especially among those with massive hemoptysis or advanced lung disease. Our results suggest that hemoptysis functions as a useful predictor of serious outcomes in PwCF and may be important to incorporate into risk prediction models and/or transplant decisions in CF.

Body Mass Index Recovery after Lung Transplant for Cystic Fibrosis.

Rationale: Many lung transplant recipients with cystic fibrosis (CF) have low preoperative body mass index (BMI); however, post-transplant BMI recovery is not well understood. Objectives: To evaluate BMI recovery (⩾18.5 kg/m2) among CF lung transplant recipients with low preoperative BMI and to investigate the association of survival with BMI recovery. Methods: The United Network for Organ Sharing and CF Foundation patient registries (June 2005-December 2016) were used to identify CF lung transplant recipients. Among recipients surviving ⩾1 year, Cox modeling compared post-transplant 1-year conditional survival between recipients with low (<17 and 17-18.49 kg/m2) versus normal preoperative BMI, stratified by BMI recovery. Results: Of 1,977 CF lung transplant recipients, 272 (14%) and 449 (23%) had a preoperative BMI of <17 and 17-18.49 kg/m2, respectively. For subgroups with a BMI of <17 and 17-18.49 kg/m2, 29% versus 49%, respectively, of those alive at 1 year recovered their BMI. Among recipients with low preoperative BMI, adjusted post-transplant 1-year conditional survival was worse than that in those with preoperative BMI ⩾ 18.5 kg/m2; however, BMI recovery mitigated this. Preoperative BMI < 17 kg/m2 had an adjusted hazard ratio of 1.29 (95% confidence interval [CI], 0.92-1.81) with BMI recovery versus 1.57 (95% CI, 1.09-2.25) without recovery, and preoperative BMI 17-18.49 kg/m2 had an adjusted hazard ratio of 1.28 (95% CI, 1.02-1.61) with BMI recovery versus 1.72 (95% CI, 1.14-2.59) without recovery. Conclusions: Patients with lower preoperative BMI were less likely to achieve BMI recovery within 1 year. However, for those who did, BMI recovery within 1 year after transplant was associated with longer survival.

Validation of the French 3-year prognostic score for death or lung transplant in the United States cystic fibrosis population.

In 2017, Nkam et al. published a prognostic score to predict death or lung transplant within 3 years among adult cystic fibrosis (CF) patients. Their model was developed using French CF registry data and was subsequently validated in the Canadian CF registry. We evaluated this prognostic score using data from adult patients with CF in the United States (US) CF Foundation Patient registry, combined with lung transplant records from the United Network for Organ Sharing (UNOS) Registry (2013 to 2016) (n=11,542). We found that the prognostic score had a very good discriminative index predicting death or lung transplant in the US CF population (AUC 0.88, 95% CI 0.88-0.89) with an odds ratio (OR) of 2.83 (95% CI 2.69 - 2.97) for each unit increase in the score. However, it did not provide significant additional utility over an FEV1 ≤30% of predicted as a predictor of death or lung transplant.

Satisfaction and effectiveness of opioid pain management among adults with cystic fibrosis: A mixed methods study.

BACKGROUND: Chronic pain is common among people living with cystic fibrosis (CF) and associated with worse clinical outcomes. Despite this, little is known about how pain is managed and how opioids are used to treat pain. The purpose of this convergent mixed methods study was to examine self-reported satisfaction and effectiveness of pain management strategies among a sample of adults with CF who are prescribed opioids. METHODS: We developed an online survey querying 4 domains - demographics, pain characteristics, pain communication, and management strategies. This was distributed nationally to adults with CF (n=48) via various online platforms. We obtained quantitative and qualitative responses regarding satisfaction and effectiveness of pain management. Emerged themes from qualitative data were compared with responses from quantitative survey domains. RESULTS: Participants reported high levels of satisfaction and effectiveness with their opioid pain management plans. However, qualitative themes emerged regarding fears of addiction, experiences of feeling stigmatized by the healthcare system and ineffectiveness and inefficiency of alternative therapies for adequate pain relief. CONCLUSIONS: Adults with CF reported opioids as an important component of their current pain management plans despite risks associated with opioid use. CF-specific pain management guideline development is warranted as is further research exploring pain development.

Low body mass index as a barrier to lung transplant in cystic fibrosis.

RATIONALE: Low body mass index (BMI) may influence lung transplant decisions for patients with advanced cystic fibrosis (CF) lung disease. OBJECTIVE: Determine whether patients with advanced CF lung disease and BMI ≤17 kg/m2 are less likely to be listed for lung transplant or have a higher risk of death without listing compared to those with higher BMI. METHODS: Using merged United Network for Organ Sharing and CF Foundation Patient Registries, we identified adults with onset of advanced lung disease (FEV1 ≤ 40% predicted) between May-2005 and December-2016. We analyzed survival using competing risks regression with cause-specific risks of listing for lung transplant and death without listing. BMI ≤ 17 kg/m2 was our predictor. MEASUREMENTS AND MAIN RESULTS: Among 5,121 CF patients with advanced lung disease, 23% were listed for lung transplant (n = 1,201), 23% died without listing (n = 1,190), and 44% were alive without listing (n = 2,730) as of December-2016. Patients with BMI ≤ 17 kg/m2 were less likely to be listed for transplant (HR 0.69; 95% CI 0.57, 0.83) and more likely to die without listing (HR 1.63; 95% CI 1.41, 1.88). We identified important regional variations in the likelihood of referral and listing, based on BMI. CONCLUSIONS: Patients with advanced CF lung disease and BMI ≤ 17 kg/m2 are less likely to be listed for lung transplant and have a higher risk of dying without listing, compared to those with higher BMI. Regional differences suggest access to transplant for malnourished CF patients may be limited by location.

Usability preferences of people living with cystic fibrosis about a lung transplant education website.

People living with cystic fibrosis (CF) need educational resources about lung transplant prior to engaging in shared decision making with their medical providers. We conducted a usability study to elicit preferences of people living with CF about how didactic and experiential content could be used in an educational resource to learn about lung transplant. We created two prototypes with different design features that participants used in a scenario-based task and evaluated using the System Usability Scale. We interviewed participants and analyzed the data to understand their preferences for educational content and design. Study participants indicated that didactic resource articles were important to understanding their illness trajectory, while experiential patient stories supported fear reduction and knowledge discovery. When learning about lung transplant participants stated a preference to control the amount of information they receive and preferred a combination of didactic and experiential knowledge.

Lung transplantation for interstitial lung disease.

Lung transplantation (LTx) can be a life-extending treatment option for patients with advanced and/or progressive fibrotic interstitial lung disease (ILD), especially idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis, sarcoidosis and connective tissue disease-associated ILD. IPF is now the most common indication for LTx worldwide. Several unique features in patients with ILD can impact optimal timing of referral or listing for LTx, pre- or post-transplant risks, candidacy and post-transplant management. As the epidemiology of LTx and community practices have evolved, recent literature describes outcomes and approaches in higher-risk candidates. In this review, we discuss the unique and important clinical findings, course, monitoring and management of patients with IPF and other progressive fibrotic ILDs during pre-LTx evaluation and up to the day of transplantation; the need for co-management with clinical experts in ILD and LTx is emphasised. Some post-LTx complications are unique in these patient cohorts, which require prompt detection and appropriate management by experts in multiple disciplines familiar with telomere biology disorders and infectious, haematological, oncological and cardiac complications to enhance the likelihood of improved outcomes and survival of LTx recipients with IPF and other ILDs.

Consensus document for the selection of lung transplant candidates: An update from the International Society for Heart and Lung Transplantation.

Tens of thousands of patients with advanced lung diseases may be eligible to be considered as potential candidates for lung transplant around the world each year. The timing of referral, evaluation, determination of candidacy, and listing of candidates continues to pose challenges and even ethical dilemmas. To address these challenges, the International Society for Heart and Lung Transplantation appointed an international group of members to review the literature, to consider recent advances in the management of advanced lung diseases, and to update prior consensus documents on the selection of lung transplant candidates. The purpose of this updated consensus document is to assist providers throughout the world who are caring for patients with pulmonary disease to identify potential candidates for lung transplant, to optimize the timing of the referral of these patients to lung transplant centers, and to provide transplant centers with a framework for evaluating and selecting candidates. In addition to addressing general considerations and providing disease specific recommendations for referral and listing, this updated consensus document includes an ethical framework, a recognition of the variability in acceptance of risk between transplant centers, and establishes a system to account for how a combination of risk factors may be taken into consideration in candidate selection for lung transplantation.

Enhancing care for individuals with advanced cystic fibrosis lung disease.

While remarkable advances in cystic fibrosis (CF) care have led to improvements in survival and quality of life, many individuals with CF are living with advanced cystic fibrosis lung disease (ACFLD) and others will face continued disease progression and its associated complex treatments and choices. This review will provide a summary of recently published guidelines for ACFLD care and lung transplant referral and highlight ongoing work to enhance the care of those with ACFLD through improvements in medical and psychosocial care, palliative care, and care around lung transplantation.

Cystic Fibrosis Foundation consensus guidelines for the care of individuals with advanced cystic fibrosis lung disease.

BACKGROUND: Advanced cystic fibrosis lung disease (ACFLD) is common, is associated with reduced quality of life, and remains the most frequent cause of death in individuals with cystic fibrosis (CF). These consensus guidelines provide recommendations to the CF community on management of both common and unique issues that arise when individuals reach a state of ACFLD. METHODS: The CF Foundation assembled a multidisciplinary expert panel consisting of three workgroups: Pulmonary management; Management of comorbid conditions; Symptom management and psychosocial issues. Topics were excluded if the management considerations did not differ in ACFLD from in the overall CF population or if already addressed in other published guidelines. Recommendations were based on a systematic literature review combined with expert opinion when appropriate. RESULTS: The committee formulated twenty-three recommendation statements specific to ACFLD that address the definition of ACFLD, pulmonary and intensive care unit management, management of selected comorbidities, symptom control, and psychosocial issues. CONCLUSIONS: These recommendations are intended to be paired with previously published management guidelines for the overall CF population, with the objective of reducing practice variability and improving overall care, quality of life, and survival in those with ACFLD.

Underweight Patients With Cystic Fibrosis Have Acceptable Survival Following Lung Transplantation: A United Network for Organ Sharing Registry Study.

BACKGROUND: Reduced BMI is an absolute contraindication for lung transplantation (LTx) at most centers in the United States. The objective of this study was to quantify post-LTx survival of moderate to severely underweight patients with cystic fibrosis (CF) (BMI < 17 kg/m2) in the United States relative to normal-weight recipients with CF and other frequently transplanted patient cohorts. METHODS: Using United Network for Organ Sharing Registry data (undergoing transplant from June 2005-November 2015), Kaplan-Meier estimates of median posttransplant survival were calculated for all patients with CF, COPD, and idiopathic pulmonary fibrosis (IPF), as well as low and normal weight CF subgroups. Cox regression modeling stratified according to transplant center assessed risk of posttransplant mortality in recipients with CF and a BMI < 17 kg/m2 compared with recipients with COPD (reference). RESULTS: Median posttransplant survival (95% CI) for CF, COPD, and IPF was 7.9 (7.2-8.6), 5.9 (5.6-6.2), and 5.5 (5.2-5.8) years, respectively. Although an absolute decrease was noted in posttransplant survival for recipients with CF and a BMI < 17 kg/m2, compared with those with CF and a BMI ≥ 17 kg/m2 (7.0 years [4.5-7.9] vs 8.2 years [7.3-9.0]), Cox modeling found no increased mortality risk (adjusted hazard ratio, 1.09; 95% CI, 0.90-1.32; P = .38). There was no difference in posttransplant mortality between patients with CF and a BMI < 17 kg/m2 and recipients with COPD and all BMIs (adjusted hazard ratio, 1.04; 95% CI, 0.86-1.25; P = .71). CONCLUSIONS: Transplant recipients with CF and a BMI < 17 kg/m2 had posttransplant survival rates comparable to those of other groups frequently undergoing transplantation. BMI < 17 kg/m2 as a single risk factor in the CF population should not be treated as an absolute contraindication to LTx.